NPASS Compound

Natural Product: NPC218856

Natural Product ID	NPC218856
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(7R,8R)-Polysphorin
IUPAC Name	(1R,2R)-2-[2,6-dimethoxy-4-[(E)-prop-1-enyl]phenoxy]-1-(3,4,5-trimethoxyphenyl)propan-1-ol
Synonyms	(7R,8R)-Polysphorin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1928007
PubChem CID	6439400
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 60 61 0 0 0 0 0 0 0 0999 V2000 7.9971 2.1594 0.5734 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6883 1.4151 0.6789 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8950 1.2564 -0.3373 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6277 0.5574 -0.3154 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1116 -0.0304 0.8133 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8856 -0.7056 0.8325 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4178 -1.2817 2.0139 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1964 -1.1752 3.1883 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1609 -0.7855 -0.3342 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6578 -0.2081 -1.4645 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8832 0.4653 -1.4775 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9676 -0.2665 -2.6470 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4233 0.3071 -3.8555 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9672 -1.4423 -0.3181 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2964 -0.8925 -0.0152 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3196 -1.2717 -1.0185 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6835 -0.7912 -0.6807 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0450 0.5070 -0.9492 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2906 1.0433 -0.6703 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6268 2.3607 -0.9536 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6301 3.1691 -1.5554 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1806 0.1619 -0.0841 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8454 -1.1441 0.1962 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5955 -1.6358 -0.0980 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7780 -2.0023 0.7905 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4881 -3.3376 1.0967 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4538 0.6348 0.2241 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6921 1.2127 1.4936 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0010 -0.8307 -2.2918 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6520 -1.3677 1.3854 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8311 3.1824 0.9291 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3905 2.0964 -0.4653 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6995 1.6307 1.2517 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4153 1.0061 1.6394 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2273 1.6946 -1.2847 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6779 0.0321 1.7254 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6372 -1.6064 4.0385 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4570 -0.1242 3.3995 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1596 -1.7305 3.1089 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2350 0.9049 -2.3890 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7988 -0.0121 -4.7218 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4888 0.0473 -4.0782 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3585 1.4084 -3.7626 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2406 0.2223 0.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3687 -2.3913 -1.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3375 1.2135 -1.4167 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2757 2.7279 -2.5124 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7467 3.3023 -0.9061 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0954 4.1471 -1.8237 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3504 -2.6726 0.1317 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2163 -3.7822 1.8047 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5056 -3.3728 1.6536 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3456 -3.8977 0.1737 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8634 1.9159 1.7702 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6105 1.8305 1.4625 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7737 0.4438 2.2902 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7636 0.1145 -2.3503 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2482 -0.6497 2.1245 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1871 -2.3460 1.6158 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7483 -1.4164 1.5393 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 6 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 9 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 22 27 1 0 27 28 1 0 16 29 1 0 15 30 1 0 11 4 1 0 24 17 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 3 35 1 0 5 36 1 0 8 37 1 0 8 38 1 0 8 39 1 0 11 40 1 0 13 41 1 0 13 42 1 0 13 43 1 0 15 44 1 1 16 45 1 6 18 46 1 0 21 47 1 0 21 48 1 0 21 49 1 0 24 50 1 0 26 51 1 0 26 52 1 0 26 53 1 0 28 54 1 0 28 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 30 59 1 0 30 60 1 0 M END

Standard InCHIKey	FLBWVIKFCMUTDS-UGZSOSCUSA-N
Standard InCHI	InChI=1S/C23H30O7/c1-8-9-15-10-17(25-3)23(18(11-15)26-4)30-14(2)21(24)16-12-19(27-5)22(29-7)20(13-16)28-6/h8-14,21,24H,1-7H3/b9-8+/t14-,21+/m1/s1
SMILES	C/C=C/c1cc(OC)c(c(c1)OC)O[C@@H]([C@@H](c1cc(OC)c(c(c1)OC)OC)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	418.2	Volume:	432.328 ? Van der Waals volume.
Dense:	0.967	LogP:	2.57 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.897 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.813 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	13.0
TPSA:	75.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.618	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.221	Fsp³:	0.391
MCE-18:	32.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.163	Fluc inhibitor:	0.404 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.131 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.275 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.334	Promiscuous compounds:	0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.99	MDCK Permeability:	-4.729
Pgp-inhibitor:	0.346	Pgp-substrate:	0.041
PAMPA:	0.017 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.06	30% Bioavailability (F30%):	0.006
50% Bioavailability (F50%):	0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.903	MRP1:	0.999
Plasma Protein Binding (PPB):	88.691%	Volume Distribution (VD):	0.057
Fu:	8.079% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.856
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.534
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.035	CYP1A2-substrate:	0.311
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.146
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.078
CYP2D6-inhibitor:	0.041	CYP2D6-substrate:	0.016
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.742
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.473 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

7.868

Half-life (T1/2):

1.11

ADMET: Toxicity

hERG Blockers:	0.236	hERG Blockers (10um):	0.417
Human Hepatotoxicity (H-HT):	0.803	Drug-induced Liver Injury (DILI):	0.597
AMES Toxicity:	0.308	Rat Oral Acute Toxicity:	0.361
Maximum Recommended Daily Dose:	0.613	Skin Sensitization:	0.797
Carcinogencity:	0.458	Eye Corrosion:	0.007
Eye Irritation:	0.537	Respiratory Toxicity:	0.675
Drug-induced Neurotoxicity:	0.851	Ototoxicity:	0.506
Hematotoxicity:	0.489	Drug-induced Nephrotoxicity:	0.583
Genotoxicity:	0.321	RPMI-8226 Immunitoxicity:	0.298
A549 Cytotoxicity:	0.498	Hek293 Cytotoxicity:	0.543
BCF:	2.197 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.759 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.378 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.548 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	rhizome	n.a.	PMID[21936523]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[21936523]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[22951040]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5681	Acorus gramineus	Species	Acoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	4
Activity	1

Activity Type	# Activity
Cell line	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[21936523]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	>	10000.0	nM	PMID[21936523]
NPT147	Cell line	SK-MEL-2	Homo sapiens	IC50	>	10000.0	nM	PMID[21936523]
NPT34	Cell line	BV-2	Mus musculus	IC50	>	200000.0	nM	PMID[21936523]
NPT34	Cell line	BV-2	Mus musculus	Activity	=	101.1	%	PMID[21936523]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC218856 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	22853
0.1-0.2	24690
0.2-0.3	2105
0.3-0.4	158
0.4-0.5	22
0.5-0.6	13
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC210623
1.0	High Similarity	NPC226788
0.8	Intermediate Similarity	NPC172818
0.7955	Intermediate Similarity	NPC470258
0.7556	Intermediate Similarity	NPC273295
0.7556	Intermediate Similarity	NPC222004
0.7556	Intermediate Similarity	NPC602870
0.6939	Remote Similarity	NPC485478
0.6667	Remote Similarity	NPC202582
0.6667	Remote Similarity	NPC243749
0.625	Remote Similarity	NPC94276
0.625	Remote Similarity	NPC109822
0.625	Remote Similarity	NPC605984
0.6216	Remote Similarity	NPC203924
0.5833	Remote Similarity	NPC474119
0.5652	Remote Similarity	NPC601172
0.5532	Remote Similarity	NPC89521
0.5472	Remote Similarity	NPC25695
0.5455	Remote Similarity	NPC483401
0.5385	Remote Similarity	NPC190629
0.5385	Remote Similarity	NPC354196
0.5283	Remote Similarity	NPC184447
0.5192	Remote Similarity	NPC473091
0.5179	Remote Similarity	NPC58607
0.5179	Remote Similarity	NPC191037
0.5179	Remote Similarity	NPC178284
0.5098	Remote Similarity	NPC79184

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC218856 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4793
0.1-0.2	4223
0.2-0.3	124
0.3-0.4	10
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data